An Anticaries Vaccine: Report on the Status of Research

Abstract

The state of the art of the research on a vaccine against dental caries has been reviewed. The subject has been analysed both from the biological and from the public health point of view. It is concluded that Streptococcus mutans plays a key role for the development of dental caries and that a vaccine directed against this microorganism could be a valuable adjunct to existing preventive measures in some countries. In others it could be a major public health measure. The unique characteristics of dental caries partly explain why a vaccine is not yet available. Protection against dental caries by immunization could be achieved by protective antibodies from serum, by IgA antibodies in saliva or by a combined effect of serum and salivary components. In rodents both peroral and parenteral immunization has provided protection against S. mutans infection and dental caries. In primates only parenteral immunization has given positive results. In humans peroral immunization has led to an increased salivary antibody activity in some studies but not in others. There is no conclusive evidence which shows that antibodies against S. mutans can influence dental caries activity in man. As structures on the cell surface of S. mutans cross-react with human tissue much work has been concentrated on identification of candidate antigens. Some of these have been purified and tested in vitro and in animal systems. Some protein antigens have given a clear-cut caries protection in primates and one of these has been produced in large amounts and is ready for testing in humans. Another candidate antigen, the enzyme complex called glucosyltransferase has shown protection in rodents and the effect of peroral administration of this antigen is now being tested in man. A considerable amount of knowledge has been obtained and the activity in the research area is high. Some groups have focused on basic immunology and have little understanding of the disease. In other groups the reverse is true. A consequence of this is that collaborative studies ought to be organized. By such studies key information about the possible role of antibodies in the development of dental caries in man could be obtained within a reasonable period of time.

Caries Development in Children in Relation to the Presence of Mutans Streptococci in Dental Plaque and of Serum Antibodies against Whole Cells and Protein Antigen I/II of Streptococcus mutans

“…IgG antibodies against SA I/II are reported to be protective against dental caries in immunized mon keys [Krasse et al, 1987] and in human adults with low caries experience [Challacombe et al, 1984]. We found no significant differences in total specific an tibodies between MS-positive and -negative groups.…”

“…The main source of infection is usually maternal saliva [Ber kowitz et ai., 1981;Berkowitz and Jones, 1985;Köhler and Bratthall, 1978;Masuda et ai., 1985] and high ma ternal salivary S. mutans levels (> 105cfu/ml) en hance its colonization [Berkowitz et al, 1981]. It has also been shown that the earlier the colonization by S. mutans, the more prone the children are to dental caries [Alaluusua and Renkonen, 1983;Köhler et al, 1988], Specific antibodies of secretory IgA isotype (in sal iva, milk or tears) and of IgG, IgM and IgA isotypes (in serum and crevicular fluid) against MS are found in most adults, but no consistent correlation between antibodies and caries prevalence among adults has been found [reviews in Brandtzaeg, 1983;Krasse et al, 1987], Also, studies on the possible association be tween antibodies and dental caries in children have proved equivocal [Tenovuo, 1986], In children, natu rally occurring salivary IgA antibodies seem to offer no protection against colonization of MS and/or against dental caries [Camling and Köhler, 1987;Ri viere and Papagiannoulis, 1987;Tenovuo et al, 1987;Aaltonen et al, 1988] whereas specific serum IgG an tibodies against S. mutans are often associated with low caries activity Aaltonen et al, 1987;Tenovuo et al, 1987]. Most of these analyses have been done using whole cells of S. mutans as anti gens which may lead to erroneous results because of possible cross-reactivity between various oral bacte ria, particularly streptococci [Bammann and Gib bons, 1979;Luo et al, 1988],…”

The genus Streptococcus

“…The search for a caries vaccine, based on S. mutans antigens, has produced a large amount of valuable and interesting experimental data which have helped to develop understanding of the caries process and of immune responses in the mouth (Krasse et al, 1987;Russell and Johnson, 1987;Klein and Scholler, 1988). However, despite successful results in experimental animals, no human trials of active immunization with such vaccines have so far been reported.…”

Antimicrobial Strategies in the Prevention of Dental Caries

“…These antigens in clude glycosyltransferases and wall-associated proteins, such as antigen I/II (also known as antigen B and P|) and antigen A [Russell and Johnson. 1987;Krasse et al, 1987]. Antigen I/II has the advantage that it is found in all MS. but it has also been implicated in cross-reactions with human heart tissue.…”